rs2839181

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003906.5(MCM3AP):c.2931T>C(p.His977His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 1,610,844 control chromosomes in the GnomAD database, including 171,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 16869 hom., cov: 32)

Exomes 𝑓: 0.46 ( 154885 hom. )

Consequence

MCM3AP
NM_003906.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.256

Variant links:

Genes affected

MCM3AP (HGNC:6946): (minichromosome maintenance complex component 3 associated protein) The minichromosome maintenance protein 3 (MCM3) is one of the MCM proteins essential for the initiation of DNA replication. The protein encoded by this gene is a MCM3 binding protein. It was reported to have phosphorylation-dependent DNA-primase activity, which was up-regulated in antigen immunization induced germinal center. This protein was demonstrated to be an acetyltransferase that acetylates MCM3 and plays a role in DNA replication. The mutagenesis of a nuclear localization signal of MCM3 affects the binding of this protein with MCM3, suggesting that this protein may also facilitate MCM3 nuclear localization. This gene is expressed in the brain or in neuronal tissue. An allelic variant encoding amino acid Lys at 915, instead of conserved Glu, has been identified in patients with mild intellectual disability. [provided by RefSeq, Jan 2014]

MCM3AP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 21-46266025-A-G is Benign according to our data. Variant chr21-46266025-A-G is described in ClinVar as [Benign]. Clinvar id is 403075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-46266025-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.256 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCM3AP	NM_003906.5 link	c.2931T>C	p.His977His	synonymous_variant	Exon 11 of 28	ENST00000291688.6	NP_003897.2	O60318-1
MCM3AP	XM_005261203.5 link	c.2931T>C	p.His977His	synonymous_variant	Exon 12 of 29		XP_005261260.1	O60318-1
MCM3AP	XM_005261204.6 link	c.2931T>C	p.His977His	synonymous_variant	Exon 12 of 29		XP_005261261.1	O60318-1
MCM3AP	XM_005261205.5 link	c.2931T>C	p.His977His	synonymous_variant	Exon 12 of 29		XP_005261262.1	O60318-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MCM3AP	ENST00000291688.6 link	c.2931T>C	p.His977His	synonymous_variant	Exon 11 of 28	1	NM_003906.5	ENSP00000291688.1	O60318-1
MCM3AP	ENST00000397708.1 link	c.2931T>C	p.His977His	synonymous_variant	Exon 12 of 29	5		ENSP00000380820.1	O60318-1
MCM3AP	ENST00000486937.5 link	n.1223T>C		non_coding_transcript_exon_variant	Exon 2 of 18	2
MCM3AP	ENST00000496607.5 link	n.928T>C		non_coding_transcript_exon_variant	Exon 1 of 18	2

Frequencies

GnomAD3 genomes

AF:

0.468

AC:

71047

AN:

151866

Hom.:

16862

Cov.:

show subpopulations

Gnomad AFR

AF:

0.501

Gnomad AMI

AF:

0.272

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.450

GnomAD3 exomes

AF:

0.457

AC:

114341

AN:

249964

Hom.:

26962

AF XY:

0.450

AC XY:

60781

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.505

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.477

Gnomad EAS exome

AF:

0.284

Gnomad SAS exome

AF:

0.390

Gnomad FIN exome

AF:

0.484

Gnomad NFE exome

AF:

0.458

Gnomad OTH exome

AF:

0.469

GnomAD4 exome

AF:

0.458

AC:

668527

AN:

1458862

Hom.:

154885

Cov.:

AF XY:

0.455

AC XY:

330023

AN XY:

725486

show subpopulations

Gnomad4 AFR exome

AF:

0.501

Gnomad4 AMR exome

AF:

0.556

Gnomad4 ASJ exome

AF:

0.482

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.391

Gnomad4 FIN exome

AF:

0.480

Gnomad4 NFE exome

AF:

0.464

Gnomad4 OTH exome

AF:

0.457

GnomAD4 genome

AF:

0.468

AC:

71074

AN:

151982

Hom.:

16869

Cov.:

AF XY:

0.467

AC XY:

34676

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.501

Gnomad4 AMR

AF:

0.501

Gnomad4 ASJ

AF:

0.469

Gnomad4 EAS

AF:

0.285

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.487

Gnomad4 NFE

AF:

0.460

Gnomad4 OTH

AF:

0.447

Alfa

AF:

0.464

Hom.:

21235

Bravo

AF:

0.471

Asia WGS

AF:

0.334

AC:

1166

AN:

3478

EpiCase

AF:

0.462

EpiControl

AF:

0.452

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.47

DANN

Benign

0.34

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over